This is a competing continuation application to continue a prospective cohort study of breast cancer prognosis, the Pathways Study. The Pathways Study is an ongoing study that is currently enrolling and following women who are newly-diagnosed with breast cancer, and takes its name from the idea that each woman diagnosed with breast cancer follows her own path. This cohort study was begun in part because little is known regarding whether lifestyle factors such as diet, physical activity, or use of complementary and alternative therapies may influence breast cancer prognosis. This is despite the substantial interest in this area among women with breast cancer, their families, and their health care providers. An additional focus was on the role of molecular markers, including genetic factors and epigenetic modification of tumor DNAs, on breast cancer prognosis. These continue to be a major focus of this research program. With the recognition that disparities in prognosis by race may be influenced in part by these factors, this application requests continuation of enrollment of women diagnosed with breast cancer into this cohort, with an emphasis on enrollment of minority participants. By the end of the fourth year of this proposed continuation, enrollment is projected to include about 550 African American women, and over 750 Asian and 700 Hispanic women, out of a cohort of over 4,300 women. Overall, about 40% of the cohort will consist of women from non-white populations. It is anticipated that over 900 deaths and 360 recurrences will occur in the Pathways Study cohort through four additional years of follow-up. In addition to following this cohort, objectives of this application are to: 1) Investigate associations of diet, physical activity, and use of complementary and alternative therapies with breast cancer recurrence and survival; 2) Examine the impact of social and built environment on prognosis, lifestyle factors, and their relationship; 3) Continue studies of methylation profiles of tumor DNAs; and 4) conduct nested case-control studies in two areas that may provide insight into racial differences in prognosis, namely the role of inflammatory and immune factors, and of vitamin D levels. The Pathways Study involves a multi-disciplinary, multi-institutional team of investigators, with a biorepository and molecular studies at Roswell Park Cancer Institute, DNA methylation studies at UCSF, and, newly proposed in this application, linkage to contextual-level databases at the Northern California Cancer Center, and continued involvement of community investigators at Zero Breast Cancer, and clinicians at KPNC. With data from interviews and questionnaires, blood samples from 89% of study participants, saliva as a source of DNA from 95%, availability of tumor blocks and clinical data from KPNC resources and databases, and the addition of contextual-level data, the Pathways Study will be a major resource for the epidemiologic investigation of breast cancer prognosis. PUBLIC HEALTH RELEVANCE: Aside from non-melanoma skin cancer, breast cancer remains the most common cancer and second largest cause of cancer deaths among women in the U.S. It is estimated that there are 2.5 million women living after a diagnosis of breast cancer in the U.S. today, and this is expected to increase in the coming years. Understanding factors that may improve prognosis for these women is a great public health importance, and the Pathways Study will enable the investigation of contextual, lifestyle, molecular, and medical care factors to decrease recurrence and improve survival for these women.